GENOME WIDE MAPPING OF LOOPS USING IN SITU HI-C Principal Investigator: Erez Lieberman Aiden Project Summary The roughly two meters of DNA in the human genome is intricately packaged to form the chromatin and chromosomes in each cell nucleus. In addition to its structural role, this organization has critical regulatory functions. In particular, the formation of loops in the human genome plays an essential role in regulating genes. We recently demonstrated the ability to create reliable maps of these loops, using an in situ Hi-C method for three-dimensional genome sequencing. Hi-C characterizes the three- dimensional configuration of the genome by determining the frequency of physical contact between all pairs of loci, genome-wide. The proposed center will apply Hi-C and other new technologies to characterize genomic loops, their regulation, and their functions. We will specifically examine these structures in a wide variety of ENCODE cell types. The principles deduced from our study will be applicable to any mammalian tissue type. Aim 1 will apply Hi-C to 80 cell types to generate maps of loops genome-wide. Aim 2 will combine Hi-C data with existing ENCODE data in order to identify the specific DNA elements responsible for establishing each loop. Aim 3 will share these datasets through our Juicebox data visualization system. The proposed project will advance our understanding of the determinants and functions of chromatin loops, provide a critical reference of loop structures in the human and mouse genomes, and present a technological framework for comprehensive analysis of genome folding in any cell type. It will also form a basis for studying the contribution of 3D genome structure to human disease and development. All data will be freely and rapidly released to the scientific community.